Drug Information Bulletin

Drug Information Centre (DIC) Indian Pharmaceutical Association

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Year

Volume: 05

Number: 38

1st January 2012

New Drug: Zonisamide The U.S. Pharmacopoeia (USP) Convention posted the following notices on its Web site IPA asks health ministry to delete additional qualifications in Recruitment Rules for the recruitment of DCGI FDA releases draft guidance on Medical Device applications Statins may be linked to reduced risk of dying from Prostate Cancer Forthcoming Event

Content

New Drug: Zonisamide 25 mg, 50 mg and 100 mg capsules Approved indication: partial seizures Many adults with refractory epilepsy have partial seizures which may or may not become generalised. When monotherapy fails, it can be difficult to decide which adjunctive treatment will help the patient. Zonisamide adds to the list of drugs such as gabapentin, lamotrigine, tiagabine and topiramate, which can be used as add-on therapy. While it is a new drug in Australia, zonisamide has been available for many years in Japan. Zonisamide is a sulfonamide, but its mechanism of action in epilepsy is uncertain. It may stabilise neuronal membranes by blocking sodium and calcium channels. Zonisamide is also a weak inhibitor of carbonic anhydrase.

The capsules are well absorbed and food does not affect bioavailability. Zonisamide has a long half-life so it takes up to 14 days for its concentration to reach a steady state. The dose should therefore not be increased at intervals of less than one week. Treatment begins with twice-daily doses, but patients can switch to once daily after the dose has been titrated to an effective level. Most of the dose is excreted in the urine as unchanged drug and metabolites, so clearance falls with declining renal function. Doses may therefore need to be titrated more slowly in patients with renal or hepatic impairment. The metabolism of zonisamide includes cytochrome P450 3A4 so there is a potential for interactions with other drugs acting on this enzyme system. Clearance is increased by phenytoin, sodium valproate and carbamazepine. Zonisamide may possibly interact with

2 carbonic anhydrase inhibitors such topiramate. as Frequent adverse effects with zonisamide include somnolence, dizziness and anorexia. Some patients lost weight during the trials.1,3 Adverse neurological events include ataxia, nystagmus, agitation and altered cognitive function. Driving skills may be impaired. Zonisamide can cause rashes, including Stevens-Johnson syndrome. The product information states that it is contraindicated if the patient has an allergy to sulfonamides. Prescribers may need to consider monitoring renal function as zonisamide has been associated with increases in urea and creatinine concentrations. Patients should be advised to maintain their hydration in warmer weather as oligohydrosis and hyperthermia have been reported (mainly in children). Early development of the drug in the USA was halted because 3.5% of patients developed kidney stones.1 Zonisamide is teratogenic in animals and is not approved for use in children. Although zonisamide reduces seizure frequency more than placebo, few patients will become free of seizures. Depending on the dose, a greater than 50% reduction in the frequency of all seizures is achieved by 3053% of patients. References* 1. Faught E, Ayala R, Montouris GG, Leppik IE; Zonisamide 922 Trial Group. Randomized controlled trial of zonisamide for the treatment of refractory partial-onset seizures. Neurology 2001; 57:1774-9 . 2. Sackellares JC, Ramsay RE, Wilder BJ, Browne TR, Shellenberger MK. Randomized, controlled clinical trial of zonisamide as adjunctive treatment for

A study in the USA compared zonisamide with placebo in 203 patients with refractory partial seizures. Different regimens were used to titrate the dose, but all patients randomised to take zonisamide were on 400 mg daily from the eighth week of the study. Patients continued their usual antiepileptic drugs. In the month before randomisation the median frequency of partial seizures was 13 in the placebo group and 1113 in the zonisamide groups. During weeks 812 of the study, the median frequency of all seizures was reduced by 9% in the placebo group and by 40.5% in the zonisamide group.1 Another American study randomised 152 patients to add zonisamide or a placebo to their usual treatment for 12 weeks. The dose of zonisamide was titrated over four weeks to 400600 mg daily. The baseline median frequency of seizures was approximately nine per month, but there was a 25.5% reduction after patients took zonisamide. In the placebo group there was a 6.6% increase in seizure frequency.2 In a European study 347 patients added a placebo or one of three doses of zonisamide to their usual therapy. The fixed-dose phase of the trial lasted for 18 weeks. During this phase, seizure frequency reduced by 17.4% in the placebo group and by 38.5% in patients taking zonisamide 300 mg daily. The efficacy of zonisamide 100 mg was not statistically different from placebo. While the median reduction in seizure frequency with zonisamide 500 mg was 46.1%, the response probably does not greatly increase above a daily dose of 400 mg.3

refractory partial seizures. Epilepsia 2004; 45:610-17. 3. Brodie MJ, Duncan R, Vespignani H, Solyom A, Bitenskyy V, Lucas C. Dosedependent safety and efficacy of zonisamide: a randomized, doubleblind, placebo-controlled study in patients with refractory partial seizures. Epilepsia 2005; 46:31-41.
Source: Aust Prescr 2011; 34:55-9

3 engaged in various facets of the profession of pharmacy, has demanded to the ministry to delete the additional qualifications mentioned in the RR of the ministry for the recruitment of DCGI. Taking strong exception to the ministry's decision to include additional qualifications for the recruitment of DCGI, the IPA said that such qualifications are inconsistent to the Rule 49A and Rule 50A of the Drugs and Cosmetics Rules 1945 made under the Drugs & Cosmetics Act, 1940 (D&C Act). Inclusion of such qualification is not in the interest of the nation, as well as the pharmacy profession. Pharmacists, by education and training are uniquely equipped and competent to handle, monitor and control the regulation, production, quality, storage and distribution of pharmaceuticals, an IPA letter to the health ministry said. In the letter, IPA general secretary SD Joag said, the qualification for the Drug Licensing and Controlling Authority is a vital issue to the pharmacy profession and in this regard we would like to bring to your kind notice that the qualification for the Licensing Authority and Controlling Authority has been mentioned in Rule 49A and Rule 50A of the Drugs and Cosmetics Rules 1945 made under the Drugs & Cosmetics Act, 1940. The qualification clause in the D&C Rules does not demand a post graduate in chemistry for DCGI post. But, the new RR seeks applications from those who are possessing post graduate degree in chemistry, biochemistry and pharmaceutical chemistry in addition to the prescribed qualifications in the Act. The union health ministry had come out with a new RR for the recruitment of the DCGI in June this year. As per the new RR, the applicant should be a graduate degree

The U.S. Pharmacopeial (USP) Convention posted the following notices on its Web site * Eight New Revision Bulletins - <711> Dissolution (posted 29-Dec2011; official 01-Feb-2012) - Galantamine Tablets (posted 29-Dec2011; official 01-Jan-2012) - Indomethacin Extended Release Capsules (posted 29-Dec-2011; official 01Jan-2012) - Lithium Hydroxide (posted 29-Dec2011; official 01-Jan-2012) - Losartan Potassium (posted 29-Dec2011; official 01-Jan-2012) - Primaquine Phosphate (posted 29Dec-2011; official 01-Jan-2012) - Venlafaxine Hydrochloride ExtendedRelease Capsules (posted 29-Dec-2011; official 01-Jan-2012) - Zaleplon (posted 29-Dec-2011; official 01-Jan-2012) IPA asks health ministry to delete additional qualifications in Recruitment Rules for the recruitment of DCGI Close on the heels of the Madras High Court's order staying the Recruitment Rule (RR) framed by the Union health ministry for the recruitment of Drugs Controller General of India (DCGI), the Indian Pharmaceutical Association (IPA), the national professional body of pharmacists

4 in pharmacy or pharmaceutical chemistry or in medicine with specialization in clinical pharmacology or microbiology from a recognized university established in India be law; postgraduate degree in pharmacy/ pharmaceutical chemistry/biochemistry/chemistry/microbio logy/ pharmacology from a recognized University or equivalent; and 15 years experience in manufacture or testing of drugs in a concern of repute or enforcement of the provisions of the Drugs and Cosmetics Act, 1940 and Rules. We therefore request you to take necessary steps to delete the qualifications namely Post graduate in Biochemistry/Chemistry/Pharmacology from the above referred GR [GSR 6 2 [E) dated 14/6/2011] for the recruitment of Drugs Controller [India], in the interest of the nation and the pharmacy profession, the IPA in its letter to the health ministry said.
Source: Pharmabiz.com

of statins may be linked to a lower risk of death from prostate cancer. Investigators looked at data on 380 individuals who had died from prostate cancer and data on 380 men who did not have prostate cancer or who had cancer that was not lethal. The investigators found that those who had died from prostate cancer were about 50% as likely to have used a statin compared to the other men. Forthcoming Event:

FDA releases draft guidance Medical Device applications

on

The Hill reports in its "Health watch" blog that the Food and Drug Administration "unveiled draft guidance Wednesday on how it reviews applications for low-risk medical devices." Noting that the agency "has been working with industry and patient advocacy groups to overhaul its socalled 510(k) program, which medical device makers complain has grown too complicated and uncertain," the account adds that the draft guidance "is not final and is not currently in effect, but gives stakeholders a chance to comment" by April 26 as the FDA begins work on its final guidance. Statins may be linked to reduced risk of dying from Prostate Cancer Reuters reports that, according to a study published online in the journal Cancer, use

12 International Congress of Ethnopharmacology February 17-19, 2012, Kolkata, India Jointly Organized by: Jadavpur University, Kolkata & International Society of Ethnopharmacology
Venue: Science City J.B.S Haldane Avenue, Kolkata www.ise-snpsju.org Inaugurater: His Excellency Dr. A. P. J. Abdul Kalam, former president of India Keynote speaker: Prof. Luc Montagnier, the Nobel laureate in Medicine

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ISE-2012